The present invention belongs to the field of physics and medicine, or more precisely, to methods and apparatus for obtaining information about physiological processes taking place in living organisms. It relates to a method of living organism state diagnosis and apparatus for its realization which could be used for the investigation and diagnosis of the functional dynamics of a living organism's physiological processes.
Functional dynamics is defined as a measure of the homestatic stability of a living organism. Functional diagnosis means using a measure or measures of functional dynamics to diagnose possible pathological conditions in a living organism. Using functional diagnosis as a diagnostic procedure has the potential to detect early precursors of pathology by revealing subtle disturbances in the relationships between physiological systems. Early detection of a pathological condition makes likelier the avoidance of non-reversible disturbances in a living organism and therefore avoids radical treatment methods. For this reason, methods of early functional diagnostics are acquiring increasing significance for population screening and development of preventive medicine.
The state of living organism is reflected in the continuous functional dynamics of its biological tissues. These dynamics are determined by the functioning of the main distributed physiological systems, such as cell metabolism, which supplies the tissues with energy, and microcirculation, which supplies their metabolic resources. The functional status of these main life supporting tissue systems is determined by distributed regulatory mechanisms, which function both for the whole organism and at the cellular level. Cell metabolism is connected with microcirculation via one important distributed tissue system-perfusion. Since the perfusion system interconnects the first two systems, study of the functional dynamics of the perfusion system will reveal important information on the state of the living organism both for the whole organism and at the cellular level.
The state of the whole-organism systems is reflected not only and not exclusively by tissue functional dynamics at separate organism sites, but mainly by the degree and the character of the spatial synergy of these dynamics. To explore this synergy of tissue physiological processes characterizing the whole-organism functional status, the investigation of continuous spatial distribution of functional dynamics of microcirculation is necessary. In the relaxation state, for example, spatial synergy of the functional dynamics in the process of tissue activity is minimal, whereas it is greatly increased under the stress conditions.
Each physiological parameter has its own physical image, or physical "projection".
Integral cell metabolism and microcirculation intensity in each organism site is reflected by its temperature value. In addition, one of the most informative physical parameters, reflecting the state of biological tissues of a living organism, is their complex dielectric permeability. Its imaginary part, the absorption coefficient of electromagnetic (EM) radiation by biological media, is characterized by a specific spectral dependence in the optical range on the main physiological agent of microcirculation--hemoglobin and its different functional forms: oxy-hemoglobin and carboxy-hemoglobin, as well as for cytochrome aa3, which also participates in cell metabolism. In a very wide range of EM-radiation frequencies, the real part of dielectric permeability depends on the degree of blood content in tissues and characterizes tissue functional inhomogeneity, produced, for example, by microcirculation dynamics.
In order to measure the temperature and dielectric characteristics of biological tissues, different physical methods are applied for functional diagnostics investigations. For non-invasive measurements of biological tissues' temperature, their electromagnetic thermal radiation is registered. The latter is the most intensive in the middle infrared (IR) range, which makes it possible to measure tissues temperature with the necessary accuracy of 0.1 degree. This is the essence of infrared dynamic thermovision, which permits investigation of spatial distribution of living organism tissue functional dynamics.
In this method, (Godik E., Gulyaev, "Functional Imaging of the Human Body," IEEE Engineering in Medicine and Biology," 1991) temporary changes in spatial distribution of IR-thermal radiation intensity of living organism tissues are registered, reflecting their spatial-temporal microcirculation dynamics in the form of a temporal sequence of thermoimages. This is performed both in the process of natural organism functioning and in the process of physiological reactions on different functional probes: reflective and humoral ones. For example, pain reactions or the influence of pharmaceutical treatments can be visualized via such procedures; the regions with different regulation disturbances can be revealed, differentially diagnosing which type of regulation is disturbed: reflective or humoral one. Also, the state of internal organs can be estimated by specific reactions of the corresponding dermatomes (Zakharjin-Ged skin zones). However, IR-thermovision method has a number of significant restrictions, as outlined below.
First, IR-thermal radiation carries direct information on physiological processes only in skin, since its characteristic absorption depth does not exceed 100.mu.. The method taught by Jobsis in U.S. Pat. No. 4,281,645 "Method and Apparatus for Monitoring Metabolism in Body Organs," attempts to overcome this limitation by transilluminating the body and integrating over a long path length. However, functional changes in blood content in skin capillary nets, disposed at the depth of 0.5.mu. or larger, are reflected in skin temperature by means of thermoprojection, due to which a delay and inertia of several seconds emerges. That is why IR-thermal radiation does not reflect practically blood flow functional dynamics, connected, for example, with cardio- and respiratory pulsation, since thermoprojection time is several seconds. Second, the temperature reflects blood flow and metabolism contributions simultaneously and integrally, which does not permit differential diagnostics of their disturbances. Third, the middle IR-range technology, necessary for the realization of the above method, is unreasonably expensive.
For dielectric permeability measurements, the investigated part of the living organism is illuminated with EM-radiation and parameters of back scattered and/ or transmitted radiation are measured. EM-radiation of optical wavelength range--from 0.3 to 1.3.mu. wavelengths is effectively used for biological tissue investigation. At near IR wavelength range from 0.65 to 1.0.mu. the tissues are transparent enough to be seen at depth of more than one centimeter. This transparency is limited by light scattering, with the characteristic weakening of such radiation making the 3-5.mu. range unusable for water-containing tissues. The absorption depths for the above mentioned physiological pigments reach up to several centimeters; in spite of the low absorption in the above region, it is selective enough to separate the contributions from the different pigments. For the wavelengths longer than 1.2.mu. the transparency of water-containing tissues decreases sharply as a result o f the strong water absorption.
The photopletismography method is well known (U.S. Pat. No. 4927244). The essence of this method is that the region under investigation, mostly the thinnest and thereby easier transilluminated body parts--ear lobes or hand and leg finger tips, are illuminated by EM-radiation of the above mentioned wavelength range; the intensity of transmitted and/or back scattered radiation is measured; the ratio of the latter intensities and that of the illuminating radiation (transmittance and back scattering coefficients, respectively) are calculated as a continuous functions of time; temporal dependencies of these coefficients, originating from cardiopulsation, arc analyzed; functional state of microcirculation is judged from the extremum positions and the amplitudes ratio. This method is similar to that taught by Parker, et al. in U.S. Pat. No. 4,576,173 "Electro-Optical Device and Method for Monitoring Instantaneous Singlet Oxygen Concentration Produced During Photoradiation Using a CW Excitation Source."
These methods, however, are based on the analysis of the microcirculation functional mechanics at separate organism sites and do not permit estimation of microcirculation over the organism surface, or the spatial picture of its interconnection within the organism scope. Thus there exists no potential to estimate the state of the organism's health based on the interaction of separate physiological systems.
More weighty information on the functional microcirculation dynamics and cell metabolism in separate organism sites could be obtained using the method of spectral monitoring of biological tissues in the near IR-wavelength range (U.S. Pat. No. 5,303,026, Strobl, et al, "Apparatus and Method for Spectroscopic Analysis of Scattering Media"). To realize this method, the part of living organism under investigation is alternatively illuminated by radiation of several wavelengths in the range from 0.6.mu. to 1.0.mu.; the intensity of transmitted and/or back scattered radiation is measured for each wavelength as a continuous function of time; coefficients of transmittance and/or back scattered radiation are determined for each wavelength; the system of differential equations is solved with the use of these data and temporal dependencies of oxyhemoglobin, carboxyhemoglobin and cytochrome aa3 are calculated. The character of these dependencies is analyzed in the process of physiological reactions on different functional tests both local ( i.e. applying a blood pressure cuff) and the whole-organism ones. The obtained dependencies are compared with similar ones for a healthy person and the presence of pathology is judged by the deviations in the reaction amplitudes and the time delays. This method permits more detailed analysis of the functional state of the living organism to be performed to reveal not only disturbances in the functional microcirculation mechanics, but also deviations in oxygenation status of the tissue investigated, in the ratio of arterial and venous blood content, in the perfusion state--by a delay in time dynamics and by the amplitude ratio of changes in oxyhemoglobin and cytochrome aa3 concentrations. This extends significantly the potential to revel pathology and its differential diagnostics.
However, this above described method as well as the previous one permits estimation of the character of functional dynamics of physiological processes only at separate organism points and does not make it possible to visualize and to investigate a continuous spatial synergy of these processes in a whole organ or in the organism as whole.
A method and apparatus are known which permit the determination of the optical properties of living organism tissues (U.S. Pat. No. 4,515,165). To realize this method, the part of living organism under investigation, a mammary gland, for example, is illuminated by electromagnetic radiation of optical wavelength range (near IR-range), transmitted radiation is acquired and the spatial distribution of its intensity is registered. This method reveals pathological inhomogeneities in transparency of living organism tissues but only of sufficiently large size and located not too deep from the surface, and happen to be turned to the radiation detector. Tumors of the mammary gland, for example, are able to be discovered with method, as a rule, too late, when they have already reached a large size .
The method proposed by Bowen in U.S. Pat. No. 4,385,634 "Radiation-Induced Thermoacoustic Imaging" describes the possibility of increasing the spatial resolution to reveal pathological changes in tissue morphology (structure) but not in physiological dynamics.
Thus, currently used methods permit investigation of spatial synergy of the functional dynamics of physiological processes only in skin, either only morphological changes in a tissues depth in one (or a few) frame or functional changes in separate preselected points. All methods reviewed yield insufficient information for differential diagnostics based on partial contributions of microcirculation and metabolic thermoproduction. Methods that permit a detailed investigation of pre-capillary blood flow and cell metabolism only provide it at separate discrete points.